{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:33:24Z","timestamp":1783953204940,"version":"3.55.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The possibility of widespread use of a novel effective therapy for Alzheimer disease (AD) will present important clinical, policy, and financial challenges.<\/jats:p><\/jats:sec>Objective<\/jats:title>To describe how including different patient, caregiver, and societal treatment-related factors affects estimates of the cost-effectiveness of a hypothetical disease-modifying AD treatment.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this economic evaluation, the Alzheimer Disease Archimedes Condition Event Simulator was used to simulate the prognosis of a hypothetical cohort of patients selected from the Alzheimer Disease Neuroimaging Initiative database who received the diagnosis of mild cognitive impairment (MCI). Scenario analyses that varied costs and quality of life inputs relevant to patients and caregivers were conducted. The analysis was designed and conducted from June 15, 2019, to September 30, 2020.<\/jats:p><\/jats:sec>Exposures<\/jats:title>A hypothetical drug that would delay progression to dementia in individuals with MCI compared with usual care.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained.<\/jats:p><\/jats:sec>Results<\/jats:title>The model included a simulated cohort of patients who scored between 24 and 30 on the Mini-Mental State Examination and had a global Clinical Dementia Rating scale of 0.5, with a required memory box score of 0.5 or higher, at baseline. Using a health care sector perspective, which included only individual patient health care costs, the ICER for the hypothetical treatment was $183\u202f000 per QALY gained. The result decreased to $173\u202f000 per QALY gained in a traditional societal perspective analysis with the inclusion of patient non\u2013health care costs. The inclusion of estimated caregiver health care costs reduced the ICER somewhat, but the inclusion of QALYs gained by caregivers led to a substantial reduction in the ICER for the hypothetical treatment, to $162\u202f000 per QALY gained in the health sector perspective. In the societal perspective scenario, with the broadest inclusion of patient and caregiver factors, the ICER decreased to $103\u202f000 per added QALY.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The findings of this economic evaluation suggest that policy makers should be aware that efforts to estimate and include the effects of AD treatments outside those on patients themselves can affect the results of the cost-effectiveness analyses that often underpin assessments of the value of new treatments. Further research and debate on including these factors in assessments that will inform discussions on fair pricing for new treatments are needed.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2021.29392","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T15:45:44Z","timestamp":1634917544000},"page":"e2129392","source":"Crossref","is-referenced-by-count":35,"title":["Evaluation of the Cost-effectiveness of Drug Treatment for Alzheimer Disease in a Simulation Model That Includes Caregiver and Societal Factors"],"prefix":"10.1001","volume":"4","author":[{"given":"Kouta","family":"Ito","sequence":"first","affiliation":[{"name":"Meyers Primary Care Institute, a joint endeavor of University of Massachusetts Medical School, Reliant Medical Group, and Fallon Health, Worcester"},{"name":"Division of Geriatric Medicine, University of Massachusetts Medical School, Worcester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Chapman","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Economic Review, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Economic Review, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tafazzoli","sequence":"additional","affiliation":[{"name":"Evidera, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco"},{"name":"San Francisco VA Medical Center, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry H.","family":"Gurwitz","sequence":"additional","affiliation":[{"name":"Meyers Primary Care Institute, a joint endeavor of University of Massachusetts Medical School, Reliant Medical Group, and Fallon Health, Worcester"},{"name":"Division of Geriatric Medicine, University of Massachusetts Medical School, Worcester"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"zoi210859r2","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.trci.2018.03.009","article-title":"Alzheimer\u2019s disease drug development pipeline: 2018.","volume":"4","author":"Cummings","year":"2018","journal-title":"Alzheimers Dement (N Y)"},{"issue":"7","key":"zoi210859r3","doi-asserted-by":"publisher","first-page":"888","DOI":"10.18553\/jmcp.2020.26.7.888","article-title":"Preclinical Alzheimer disease drug development: early considerations based on phase 3 clinical trials.","volume":"26","author":"Hung","year":"2020","journal-title":"J Manag Care Spec Pharm"},{"issue":"1","key":"zoi210859r4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1474-4422(20)30452-X","article-title":"Rapid drug access and scientific rigour: a delicate balance.","volume":"20","author":"The Lancet Neurology","year":"2021","journal-title":"Lancet Neurol"},{"issue":"10","key":"zoi210859r5","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.jalz.2019.05.004","article-title":"Assessing cost-effectiveness of early intervention in Alzheimer\u2019s disease: an open-source modeling framework.","volume":"15","author":"Green","year":"2019","journal-title":"Alzheimers Dement"},{"issue":"11","key":"zoi210859r6","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1002\/alz.v16.11","article-title":"Preparing the health-care system to pay for new Alzheimer\u2019s drugs.","volume":"16","author":"Lin","year":"2020","journal-title":"Alzheimers Dement"},{"issue":"3","key":"zoi210859r7","doi-asserted-by":"publisher","first-page":"891","DOI":"10.3233\/JAD-191055","article-title":"Quantifying and describing the natural history and costs of Alzheimer\u2019s disease and effects of hypothetical interventions.","volume":"75","author":"Wimo","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"zoi210859r8","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.trci.2018.01.001","article-title":"Alzheimer\u2019s disease Archimedes condition-event simulator: development and validation.","volume":"4","author":"Kansal","year":"2018","journal-title":"Alzheimers Dement (N Y)"},{"issue":"5","key":"zoi210859r11","doi-asserted-by":"publisher","first-page":"411","DOI":"10.2165\/11531870-000000000-00000","article-title":"Cost effectiveness of donepezil in the treatment of mild to moderate Alzheimer\u2019s disease: a UK evaluation using discrete-event simulation.","volume":"28","author":"Getsios","year":"2010","journal-title":"Pharmacoeconomics"},{"issue":"11","key":"zoi210859r12","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1007\/s40273-014-0203-5","article-title":"Evaluating disease-modifying agents: a simulation framework for Alzheimer\u2019s disease.","volume":"32","author":"Guo","year":"2014","journal-title":"Pharmacoeconomics"},{"issue":"2","key":"zoi210859r13","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/01.JGP.0000192478.82189.a8","article-title":"Mapping scores onto stages: Mini-Mental State Examination and Clinical Dementia Rating.","volume":"14","author":"Perneczky","year":"2006","journal-title":"Am J Geriatr Psychiatry"},{"issue":"6","key":"zoi210859r14","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1212\/WNL.57.6.957","article-title":"Measuring Alzheimer\u2019s disease progression with transition probabilities: estimates from CERAD.","volume":"57","author":"Neumann","year":"2001","journal-title":"Neurology"},{"issue":"1","key":"zoi210859r15","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.v6.1","article-title":"Alzheimer\u2019s disease drug development pipeline: 2020.","volume":"6","author":"Cummings","year":"2020","journal-title":"Alzheimers Dement (N Y)"},{"issue":"1","key":"zoi210859r16","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.neurobiolaging.2012.03.006","article-title":"Estimating sample sizes for predementia Alzheimer\u2019s trials based on the Alzheimer\u2019s Disease Neuroimaging Initiative.","volume":"34","author":"Grill","year":"2013","journal-title":"Neurobiol Aging"},{"issue":"1","key":"zoi210859r17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12955-017-0591-2","article-title":"How useful is the EQ-5D in assessing the impact of caring for people with Alzheimer\u2019s disease?","volume":"15","author":"Reed","year":"2017","journal-title":"Health Qual Life Outcomes"},{"issue":"4","key":"zoi210859r18","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1177\/0272989X06290495","article-title":"Preference-based EQ-5D index scores for chronic conditions in the United States.","volume":"26","author":"Sullivan","year":"2006","journal-title":"Med Decis Making"},{"issue":"2","key":"zoi210859r19","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3233\/JAD-122392","article-title":"The GERAS Study: a prospective observational study of costs and resource use in community dwellers with Alzheimer\u2019s disease in three European countries\u2014study design and baseline findings.","volume":"36","author":"Wimo","year":"2013","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"zoi210859r21","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/01.wad.0000201851.52707.c9","article-title":"Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL.","volume":"20","author":"J\u00f6nsson","year":"2006","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"2","key":"zoi210859r22","first-page":"109","article-title":"Pricing of monoclonal antibody therapies: higher if used for cancer?","volume":"24","author":"Hernandez","year":"2018","journal-title":"Am J Manag Care"},{"issue":"2","key":"zoi210859r23","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3233\/JAD-191212","article-title":"Costs of early stage Alzheimer\u2019s disease in the United States: cross-sectional analysis of a prospective cohort study (GERAS-US)1.","volume":"75","author":"Robinson","year":"2020","journal-title":"J Alzheimers Dis"},{"issue":"10","key":"zoi210859r24","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1007\/s40273-020-00942-2","article-title":"Perspective and costing in cost-effectiveness analysis, 1974-2018.","volume":"38","author":"Kim","year":"2020","journal-title":"Pharmacoeconomics"},{"issue":"5","key":"zoi210859r25","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.jval.2010.12.008","article-title":"Model-based economic evaluation in Alzheimer\u2019s disease: a review of the methods available to model Alzheimer\u2019s disease progression.","volume":"14","author":"Green","year":"2011","journal-title":"Value Health"},{"issue":"7","key":"zoi210859r26","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s40273-016-0392-1","article-title":"Systematic review of model-based economic evaluations of treatments for Alzheimer\u2019s disease.","volume":"34","author":"Hernandez","year":"2016","journal-title":"Pharmacoeconomics"},{"issue":"14","key":"zoi210859r27","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1212\/WNL.0b013e3181f6133d","article-title":"Assessment of potential measures in models of progression in Alzheimer disease.","volume":"75","author":"McLaughlin","year":"2010","journal-title":"Neurology"},{"issue":"12","key":"zoi210859r28","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/j.jval.2019.07.002","article-title":"How should we capture health state utility in dementia? comparisons of DEMQOL-Proxy-U and of self- and proxy-completed EQ-5D-5L.","volume":"22","author":"Martin","year":"2019","journal-title":"Value Health"},{"issue":"4","key":"zoi210859r29","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s40273-019-00788-3","article-title":"Family and caregiver spillover effects in cost-utility analyses of Alzheimer\u2019s disease interventions.","volume":"37","author":"Lin","year":"2019","journal-title":"Pharmacoeconomics"},{"issue":"2","key":"zoi210859r30","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1177\/0272989X15605094","article-title":"A Framework for including family health spillovers in economic evaluation.","volume":"36","author":"Al-Janabi","year":"2016","journal-title":"Med Decis Making"},{"issue":"4","key":"zoi210859r31","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1007\/s40273-018-0730-6","article-title":"The inclusion of spillover effects in economic evaluations: not an optional extra.","volume":"37","author":"Brouwer","year":"2019","journal-title":"Pharmacoeconomics"},{"issue":"12","key":"zoi210859r32","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1007\/s40273-013-0104-z","article-title":"How to include informal care in economic evaluations.","volume":"31","author":"Hoefman","year":"2013","journal-title":"Pharmacoeconomics"},{"issue":"1","key":"zoi210859r33","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1177\/0272989X14541328","article-title":"Measuring family HRQoL spillover effects using direct health utility assessment.","volume":"35","author":"Prosser","year":"2015","journal-title":"Med Decis Making"},{"issue":"2","key":"zoi210859r34","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1586\/14737167.2015.997216","article-title":"Progress in measuring family spillover effects for economic evaluations.","volume":"15","author":"Tilford","year":"2015","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"issue":"6","key":"zoi210859r35","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s40273-013-0040-y","article-title":"Disutility of illness for caregivers and families: a systematic review of the literature.","volume":"31","author":"Wittenberg","year":"2013","journal-title":"Pharmacoeconomics"},{"key":"zoi210859r37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhealeco.2020.102346","article-title":"Health technology assessment with risk aversion in health.","volume":"72","author":"Lakdawalla","year":"2020","journal-title":"J Health Econ"},{"key":"zoi210859r38","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/s12913-016-1519-y","article-title":"Economic evaluation of health promotion for older people-methodological problems and challenges.","volume":"16","author":"Huter","year":"2016","journal-title":"BMC Health Serv Res"},{"issue":"12","key":"zoi210859r39","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.jval.2018.04.1828","article-title":"Time is money: investigating the value of leisure time and unpaid work.","volume":"21","author":"Verbooy","year":"2018","journal-title":"Value Health"},{"issue":"16","key":"zoi210859r41","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1001\/jama.2019.2633","article-title":"Novel therapies for an aging population: grappling with price, value, and affordability.","volume":"321","author":"Gurwitz","year":"2019","journal-title":"JAMA"},{"issue":"8","key":"zoi210859r42","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1002\/alz.v17.8","article-title":"Generalizability of findings from a clinical sample to a community-based sample: a comparison of ADNI and ARIC.","volume":"17","author":"Gianattasio","year":"2021","journal-title":"Alzheimers Dement"},{"issue":"4","key":"zoi210859r43","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1002\/alz.v17.4","article-title":"Failure to demonstrate efficacy of aducanumab: an analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019.","volume":"17","author":"Knopman","year":"2021","journal-title":"Alzheimers Dement"},{"issue":"2","key":"zoi210859r44","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jval.2017.12.007","article-title":"Defining elements of value in health care\u2014a health economics approach: an ISPOR Special Task Force Report [3].","volume":"21","author":"Lakdawalla","year":"2018","journal-title":"Value Health"},{"key":"zoi210859r9","author":"Tafazzoli","year":"2018"},{"key":"zoi210859r20","doi-asserted-by":"crossref","DOI":"10.1093\/acprof:oso\/9780190492939.001.0001","volume-title":"Cost-effectiveness in Health and Medicine","author":"Neumann","year":"2016"},{"key":"zoi210859r1","unstructured":"Alzheimer\u2019s Association. Alzheimer\u2019s and dementia facts and figures. Accessed October 7, 2020. https:\/\/www.alz.org\/alzheimers-dementia\/facts-figures"},{"key":"zoi210859r10","unstructured":"ADNI. Alzheimer\u2019s Disease Neuroimaging Initiative. Accessed February 9, 2021. http:\/\/adni.loni.usc.edu\/"},{"key":"zoi210859r36","unstructured":"Claxton? K, Walker? S, Palmer? S, Sculpher? M. Appropriate perspectives for health care decisions. Working Papers, Centre for Health Economics, University of York. 2010. Accessed September 22, 2021. https:\/\/ideas.repec.org\/p\/chy\/respap\/54cherp.html"},{"key":"zoi210859r40","unstructured":"Chapman? R, Kumar? V, Samur? S, Zaim? R, Segel? C, Pearson? SD. Value assessment methods and pricing recommendations for potential cures: a technical brief. August 6, 2019. Accessed September 22, 2021. https:\/\/icer.org\/wp-content\/uploads\/2020\/10\/Valuing-a-Cure-Technical-Brief.pdf"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2785387\/ito_2021_oi_210859_1723210500.57974.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T15:00:35Z","timestamp":1723820435000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2785387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":44,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2021.29392","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}